PRP19_RAT
ID PRP19_RAT Reviewed; 504 AA.
AC Q9JMJ4; Q3B7C6;
DT 23-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 20-DEC-2005, sequence version 2.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Pre-mRNA-processing factor 19 {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q9UMS4};
DE AltName: Full=Neuronal differentiation-related gene protein;
DE AltName: Full=PRP19/PSO4 homolog;
DE AltName: Full=RING-type E3 ubiquitin transferase PRP19 {ECO:0000305};
GN Name=Prpf19 {ECO:0000312|RGD:708496}; Synonyms=Prp19;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH CDC5L, AND
RP SUBCELLULAR LOCATION.
RX PubMed=16352598; DOI=10.1074/jbc.m510881200;
RA Urano Y., Iiduka M., Sugiyama A., Akiyama H., Uzawa K., Matsumoto G.,
RA Kawasaki Y., Tashiro F.;
RT "Involvement of the mouse Prp19 gene in neuronal/astroglial cell fate
RT decisions.";
RL J. Biol. Chem. 281:7498-7514(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Ubiquitin-protein ligase which is a core component of several
CC complexes mainly involved pre-mRNA splicing and DNA repair. Required
CC for pre-mRNA splicing as component of the spliceosome. Core component
CC of the PRP19C/Prp19 complex/NTC/Nineteen complex which is part of the
CC spliceosome and participates in its assembly, its remodeling and is
CC required for its activity. During assembly of the spliceosome, mediates
CC 'Lys-63'-linked polyubiquitination of the U4 spliceosomal protein
CC PRPF3. Ubiquitination of PRPF3 allows its recognition by the U5
CC component PRPF8 and stabilizes the U4/U5/U6 tri-snRNP spliceosomal
CC complex. Recruited to RNA polymerase II C-terminal domain (CTD) and the
CC pre-mRNA, it may also couple the transcriptional and spliceosomal
CC machineries. The XAB2 complex, which contains PRPF19, is also involved
CC in pre-mRNA splicing, transcription and transcription-coupled repair.
CC Beside its role in pre-mRNA splicing PRPF19, as part of the PRP19-CDC5L
CC complex, plays a role in the DNA damage response/DDR. It is recruited
CC to the sites of DNA damage by the RPA complex where PRPF19 directly
CC ubiquitinates RPA1 and RPA2. 'Lys-63'-linked polyubiquitination of the
CC RPA complex allows the recruitment of the ATR-ATRIP complex and the
CC activation of ATR, a master regulator of the DNA damage response. May
CC also play a role in DNA double-strand break (DSB) repair by recruiting
CC the repair factor SETMAR to altered DNA. As part of the PSO4 complex
CC may also be involved in the DNA interstrand cross-links/ICLs repair
CC process. In addition, may also mediate 'Lys-48'-linked
CC polyubiquitination of substrates and play a role in proteasomal
CC degradation (By similarity). May play a role in the biogenesis of lipid
CC droplets (By similarity). May play a role in neural differentiation
CC possibly through its function as part of the spliceosome
CC (PubMed:16352598). {ECO:0000250|UniProtKB:Q99KP6,
CC ECO:0000250|UniProtKB:Q9UMS4, ECO:0000269|PubMed:16352598}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000250|UniProtKB:Q9UMS4};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q9UMS4}.
CC -!- SUBUNIT: Homotetramer. Component of activated, catalytic and post-
CC catalytic spliceosomes. Component of the Prp19 complex/PRP19C/Nineteen
CC complex/NTC and related complexes described as PRP19-CDC5L splicing
CC complex and PSO4 complex. A homotetramer of PRPF19, CDC5L, PLRG1 and
CC BCAS2 constitute the core of those complexes. The interaction with
CC CDC5L, PLRG1 and BCAS2 is direct within this core complex. At least
CC three less stably associated proteins CTNNBL1, CWC15 and HSPA8 are
CC found in the Prp19 complex. The Prp19 complex associates with the
CC spliceosome during its assembly and remodeling recruiting additional
CC proteins. Component of the XAB2 complex, a multimeric protein complex
CC composed of XAB2, PRPF19, AQR, ZNF830, ISY1, and PPIE. Interacts with
CC CWC22 and EIF4A3 in an RNA-independent manner. Interacts with RPA1 and
CC RPA2; the PRP19-CDC5L complex is recruited to the sites of DNA repair
CC where it interacts with the replication protein A complex (RPA).
CC Interacts with SETMAR; required for SETMAR recruitment to site of DNA
CC damage. Interacts with U2AF2; the interaction is direct and recruits
CC the Prp19 complex to RNA polymerase II C-terminal domain (CTD) and the
CC pre-mRNA. Interacts with PRPF3. Interacts with APEX1, DNTT and PSMB4.
CC Interacts with KNSTRN (By similarity). Interacts with PSMC5 (By
CC similarity). Interacts (via N-terminus) with CDC5L (PubMed:16352598).
CC Interacts with KHDC4 (By similarity). Interacts with USB1 (By
CC similarity). {ECO:0000250|UniProtKB:Q99KP6,
CC ECO:0000250|UniProtKB:Q9UMS4, ECO:0000269|PubMed:16352598}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16352598}. Nucleus,
CC nucleoplasm {ECO:0000250|UniProtKB:Q9UMS4}. Cytoplasm, cytoskeleton,
CC spindle {ECO:0000250|UniProtKB:Q9UMS4}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q9UMS4}. Lipid droplet
CC {ECO:0000250|UniProtKB:Q9UMS4}. Note=Nucleoplasmic in interphase cells.
CC Irregularly distributed in anaphase cells. In prophase cells, uniformly
CC distributed, but not associated with condensing chromosomes. Found in
CC extrachromosomal regions in metaphase cells. Mainly localized to the
CC mitotic spindle apparatus when chromosomes segregate during anaphase.
CC When nuclei reform during late telophase, uniformly distributed in
CC daughter cells and displays no preferred association with decondensing
CC chromatin. Recruited on damaged DNA at sites of double-strand break (By
CC similarity). {ECO:0000250|UniProtKB:Q9UMS4}.
CC -!- DOMAIN: The 7 WD repeats are necessary and sufficient to support
CC interaction with the RPA complex. {ECO:0000250|UniProtKB:Q9UMS4}.
CC -!- SIMILARITY: Belongs to the WD repeat PRP19 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB020022; BAA95215.2; -; mRNA.
DR EMBL; BC107669; AAI07670.1; -; mRNA.
DR RefSeq; NP_647549.2; NM_139333.3.
DR AlphaFoldDB; Q9JMJ4; -.
DR SMR; Q9JMJ4; -.
DR BioGRID; 251533; 3.
DR IntAct; Q9JMJ4; 4.
DR MINT; Q9JMJ4; -.
DR STRING; 10116.ENSRNOP00000028373; -.
DR iPTMnet; Q9JMJ4; -.
DR PhosphoSitePlus; Q9JMJ4; -.
DR jPOST; Q9JMJ4; -.
DR PaxDb; Q9JMJ4; -.
DR PeptideAtlas; Q9JMJ4; -.
DR PRIDE; Q9JMJ4; -.
DR GeneID; 246216; -.
DR KEGG; rno:246216; -.
DR UCSC; RGD:708496; rat.
DR CTD; 27339; -.
DR RGD; 708496; Prpf19.
DR VEuPathDB; HostDB:ENSRNOG00000020897; -.
DR eggNOG; KOG0289; Eukaryota.
DR HOGENOM; CLU_023894_1_1_1; -.
DR InParanoid; Q9JMJ4; -.
DR OMA; VTRVIYH; -.
DR OrthoDB; 1049599at2759; -.
DR PhylomeDB; Q9JMJ4; -.
DR Reactome; R-RNO-6781823; Formation of TC-NER Pre-Incision Complex.
DR Reactome; R-RNO-6782135; Dual incision in TC-NER.
DR Reactome; R-RNO-6782210; Gap-filling DNA repair synthesis and ligation in TC-NER.
DR Reactome; R-RNO-72163; mRNA Splicing - Major Pathway.
DR UniPathway; UPA00143; -.
DR PRO; PR:Q9JMJ4; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000020897; Expressed in skeletal muscle tissue and 20 other tissues.
DR Genevisible; Q9JMJ4; RN.
DR GO; GO:0071013; C:catalytic step 2 spliceosome; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005662; C:DNA replication factor A complex; IEA:Ensembl.
DR GO; GO:0005811; C:lipid droplet; IEA:UniProtKB-SubCell.
DR GO; GO:0016607; C:nuclear speck; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000974; C:Prp19 complex; ISS:UniProtKB.
DR GO; GO:0035861; C:site of double-strand break; ISS:UniProtKB.
DR GO; GO:0005819; C:spindle; IEA:UniProtKB-SubCell.
DR GO; GO:0005681; C:spliceosomal complex; ISO:RGD.
DR GO; GO:0071006; C:U2-type catalytic step 1 spliceosome; IBA:GO_Central.
DR GO; GO:0071007; C:U2-type catalytic step 2 spliceosome; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISS:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IBA:GO_Central.
DR GO; GO:0034450; F:ubiquitin-ubiquitin ligase activity; ISO:RGD.
DR GO; GO:0000077; P:DNA damage checkpoint signaling; ISS:UniProtKB.
DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; ISS:UniProtKB.
DR GO; GO:0008610; P:lipid biosynthetic process; ISO:RGD.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; ISS:UniProtKB.
DR GO; GO:0048711; P:positive regulation of astrocyte differentiation; IMP:RGD.
DR GO; GO:0048026; P:positive regulation of mRNA splicing, via spliceosome; ISO:RGD.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IDA:MGI.
DR GO; GO:0010498; P:proteasomal protein catabolic process; ISS:UniProtKB.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0008104; P:protein localization; ISS:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; ISO:RGD.
DR GO; GO:0000245; P:spliceosomal complex assembly; ISO:RGD.
DR GO; GO:0000244; P:spliceosomal tri-snRNP complex assembly; ISS:UniProtKB.
DR Gene3D; 2.130.10.10; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR020472; G-protein_beta_WD-40_rep.
DR InterPro; IPR013915; Pre-mRNA_splic_Prp19.
DR InterPro; IPR038959; Prp19.
DR InterPro; IPR000772; Ricin_B_lectin.
DR InterPro; IPR003613; Ubox_domain.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR43995; PTHR43995; 1.
DR Pfam; PF08606; Prp19; 1.
DR Pfam; PF04564; U-box; 1.
DR Pfam; PF00400; WD40; 5.
DR PRINTS; PR00320; GPROTEINBRPT.
DR SMART; SM00504; Ubox; 1.
DR SMART; SM00320; WD40; 7.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS51698; U_BOX; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 1.
DR PROSITE; PS50082; WD_REPEATS_2; 4.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Cytoskeleton; DNA damage; DNA repair;
KW Lipid droplet; mRNA processing; mRNA splicing; Nucleus; Reference proteome;
KW Repeat; Spliceosome; Transferase; Ubl conjugation pathway; WD repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9UMS4"
FT CHAIN 2..504
FT /note="Pre-mRNA-processing factor 19"
FT /id="PRO_0000051147"
FT DOMAIN 2..73
FT /note="U-box"
FT REPEAT 219..259
FT /note="WD 1"
FT REPEAT 262..301
FT /note="WD 2"
FT REPEAT 304..345
FT /note="WD 3"
FT REPEAT 348..387
FT /note="WD 4"
FT REPEAT 390..429
FT /note="WD 5"
FT REPEAT 433..472
FT /note="WD 6"
FT REPEAT 473..503
FT /note="WD 7"
FT REGION 68..223
FT /note="May mediate interaction with PSMC5"
FT /evidence="ECO:0000250|UniProtKB:Q99KP6"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UMS4"
FT MOD_RES 122
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9UMS4"
FT MOD_RES 179
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99KP6"
FT MOD_RES 244
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99KP6"
FT MOD_RES 261
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9UMS4"
SQ SEQUENCE 504 AA; 55239 MW; B2918188A0651024 CRC64;
MSLICSISNE VPEHPCVSPV SNHVYERRLI EKYIAENGTD PINNQPLSEE QLIDIKVAHP
IRPKPPSATS IPAILKALQD EWDAVMLHSF TLRQQLQTTR QELSHALYQH DAACRVIARL
TKEVTAAREA LATLKPQAGL IVPQAVPSSQ PSVVGAGEPM DLGELVGMTP EIIQKLQDKA
TVLTTERKKR GKTVPEELVK PEELSKYRQV ASHVGLHSAS IPGILALDLC PSDTNKILTG
GADKNVVVFD KSTEQILATL KGHTKKVTSV VFHPSQELVF SASPDATIRI WSVPNTSCVQ
VVRAHESAVT GLSLHATGDY LLSSSDDQYW AFSDIQTGRV LTKVTDETSG CSLTCAQFHP
DGLIFGTGTM DSQIKIWDLK ERTNVANFPG HSGPITSIAF SENGYYLATA ADDSSVKLWD
LRKLKNFKTL QLDNNFEVKS LIFDQSGTYL ALGGTDVQIY ICKQWTEILH FTEHSGLTTG
VAFGHHAKFI ASTGMDRSLK FYSL
